Cystic fibrosis investigators within the P30 Center require access to expertise and specialized equipment for their studies of CFTR expression and function. For both established CF laboratories and those new to CF research, a need has been identified for developing novel cell lines expressing mutant and wild type CFTR, and for dedicated equipment and biophysical protocols necessary to assess CFTR function. In particular, we propose two specific aims: Specific Aim 1. Cellular models expressing wild type and mutant CFTR will be developed and provided by Core A. These will include primary cells from murine lungs and novel lentiviral-transduced cell lines. The latter include innovative cell models useful for CFTR proteomic and structural studies and for high throughput screens to discover the next generation of CF drugs. Specific Aim 2, Assistance, equipment and expertise necessary to perform functional assays of CFTR in the above cell models (Aim 1) will include biophysical techniques (patch clamp). These assays are required to test the efficacies of new maneuvers to rescue mutant CFTR channel activity and regulation as well as to define the underlying mechanisms. The Core will aid in the development/validation of new CF cell models; provide primary murine airway epithelial cells encoding specific CFTR mutations; and assist investigators with their experiments to test the effects of new maneuvers on mutant CFTR (e.g., DeltaF508) protein stability and channel function. Collaborative studies involving proteomic studies of CFTR post-translational modifications, discovery of peptides from the first cytosolic loop of CFTR that specifically block NBD1-TMD1 binding and numerous other NIH funded projects will also be assisted by the Core. Core A will foster interdisciplinary research by providing valuable new cell models and assays of CFTR expression and function to investigators less familiar with the requisite techniques, and contribute to innovative studies of CF pathogenesis and experimental therapy.